Heterochiral Ala/(alpha Me)Aze sequential oligopeptides: Synthesis and conformational study

alpha-Amino acid residues with a phi,psi constrained conformation are known to significantly bias the peptide backbone 3D structure. An intriguing member of this class of compounds is (alpha Me)Aze, characterized by an N-alpha-alkylated four-membered ring and C-alpha-methylation. We have already reported that (S)-(alpha Me)Aze, when followed by (S)-Ala in the homochiral dipeptide sequential motif -(S)-(alpha Me)Aze-(S)-Ala-, tends to generate the unprecedented gamma-bend ribbon conformation, as formation of a regular, fully intramolecularly H-bonded gamma-helix is precluded, due to the occurrence of a tertiary amide bond every two residues. In this work, we have expanded this study to the preparation and 3D structural analysis of the heterochiral (S)-Ala/(R)-(alpha Me)Aze sequential peptides from dimer to hexamer. Our conformational results show that members of this series may fold in type-II beta-turns or in gamma-turns depending on the experimental conditions.